Nicotine has been utilized as an insecticide for many years. Yamamoto has studied a number of nicotinoids (both natural and synthetic) with regard to their insecticidal activity [Agr. Biol. Chem., 26, 709(1962); Id., 27, 445(1963); Id., 27, 450(1963); Id., 27, 684(1963); Id., 32, 568(1968); Id., 32, 747(1968); Id., 32, 1341(1968)]. Several of the analogs studied possess significant toxicity towards aphids, house flies, and cockroaches. U.S. Pat. Nos. 4,155,909; 4,321,387; and 4,332,945 describe the production of novel nicotine derivatives and the nature of their insecticidal activity.
Of the many nicotine analogs reported in the literature, the only ones having amino substituents on an intact nicotine ring skeleton are pyridine substituted derivatives, e.g., 2-amino- and 4-aminonicotine and 2-amino- and 4-aminocotinine [Heterocycles, 23, 1681(1985); Chem. Ber.,57, 1163(1924)].
U.S. Pat. No. 2,890,222 describes the production of quaternized nicotine salts such as 1-amino-1-methyl-2-(3-pyridyl)pyrrolidinium chloride. These quaternary salts have utility as insecticides, parasiticides and fungicides, and they are less toxic than nicotine to warm-blooded animals.
Other nicotine types of polyheterocyclic compounds have been found to exhibit beneficial pharmacodynamic activity in mammals. U.S. Pat. No. 3,991,197 describes pyrrolidinylpyridine compounds such as (2,2-dimethyl-5-phenyl-3-pyrrolidinyl)pyridine. Such compounds are characterized by analgesic activity.
U.S. Pat. No. 4,267,185 describes pyrrolylpiperidines such as 1,2,3,6-tetrahydro-1-methyl-4-(1-methylpyrrol-2-yl)pyridine, which are useful as antidepressant agents.
There is continuing interest in the development of pharmaceutical compositions such as psychotherapeutic agents, which are effective in low dosages without an unacceptable level of side effects. One productive approach to the development of biologically active molecules derives from the combination of structural classes or substructures from two or more types of compounds.
Accordingly, it is an object of this invention to provide a novel class of nicotine analogs and related structures.
It is another object of this invention to provide compounds which derive from the combination of tobacco alkaloid-type structures such as 2-(3-pyridyl)pyrrolidinyl-with a substituent such as 1,.omega.-diaminoalkyl.
It is a further object of this invention to provide nicotine derivatives which exhibit tranquilizing and muscle relaxing activities in mammals, without inducing nicotine-like effects such as hypertension and tachycardia.
Other objects and advantages of the present invention shall become apparent from the accompanying description and examples.